Successful Vemurafenib Treatment of Progressive BRAF V600E–Mutated Anaplastic Pleomorphic Xanthoastrocytoma


Key Points

  • A patient with a BRAF V600E–mutated glioma was successfully treated with vemurafenib monotherapy.
  • A radiographic near complete response was observed after approximately 3 weeks of treatment.

The BRAF inhibitor vemurafenib (Zelboraf) is approved for treatment of BRAF-mutated metastatic melanoma. There are reports indicating that vemurafenib may be active in the treatment of intracranial neoplasms with BRAF mutations. As reported in the Journal of Clinical Oncology, Lee et al from Brigham and Women’s Cancer Center successfully treated a BRAF V600E–mutated glioma with vemurafenib monotherapy.

Patient Course

The patient was a 41-year-old man with WHO grade 2 anaplastic pleomorphic xanthoastrocytoma with a BRAF V600E mutation who developed radiographic progression despite surgery, radiation, and treatment with temozolomide. The patient was initially observed with serial imaging for approximately 2 years until magnetic resonance imaging (MRI) showed increased surrounding enhancement. Treatment with temozolomide was followed by radiographic progression after two cycles.

A second resection showed WHO grade 3 disease, with a change in histology from the resection 3 years before, including increased cellularity, mitoses, and Ki-67 labeling index of 20%. He was treated with involved field radiation (total dose = 59.40 Gy in 47 fractions of 1.8 Gy) and concurrent temozolomide as a radiation sensitizer. Although initial postradiation imaging showed some improvement in enhancement, the lesion subsequently developed increased nodular enhancement. In order to account for potential pseudoprogression the patient was closely monitored for 6 months, but the lesion continued to expand and exhibited increase nodular enhancement and surrounding edema.

Vemurafenib Treatment

Since the patient was known to harbor a BRAF V600E mutation, the authors contacted his health insurer, who agreed to cover the cost of vemurafenib. After beginning vemurafenib at 720 mg twice daily, the patient developed grade 2 diffuse morbilliform eruption with xerosis and follicular prominence at 10 to 14 days, with workup revealing a superficial and deep perivascular lymphocytic infiltrate with rare eosinophils suggestive of a hypersensitivity reaction.

Grade 1 transaminitis was observed without other evidence of systemic hypersensitivity; the reaction was managed with topical corticosteroids and antihistamines, with eventual improvement in the skin eruption and transaminitis. Grade 1 alopecia and grade 1 diarrhea may also have been related to vemurafenib.

MRI with contrast after approximately 3 weeks of vemurafenib showed an interval decrease in nodular enhancement. MRI with contrast at approximately 12 weeks confirmed this finding and showed minimal residual enhancement and improvement in edema consistent with a nearly complete response.

The investigators noted, “[W]e successfully treated a BRAF V600E anaplastic [pleomorphic xanthoastrocytoma] with vemurafenib, and an excellent radiographic response was achieved. Further investigation of BRAF inhibitors for the treatment of BRAF-mutated primary brain tumors is warranted, and a clinical trial testing the efficacy and safety of dabrafenib (a BRAF inhibitor) and trametinib (an MEK inhibitor) in patients with BRAF V600E-mutated rare cancers, including gliomas ( NCT02034110), is in development.”

Eudocia Q. Lee, MD, MPH, of Brigham and Women’s Cancer Center, is the first author of the Journal of Clinical Oncology report.

The authors indicated no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.